title: Valproic acid-induced gene expression responses in rat whole embryo culture and comparison across in vitro developmental and non-developmental models.
abstract: Transcriptomic evaluations may improve toxicity prediction of in vitro-based developmental models. In this study, transcriptomics was used to identify VPA-induced gene expression changes in rat whole embryo culture (WEC). Furthermore, VPA-induced responses were compared across in vitro-based developmental models, such as the cardiac and neural embryonic stem cells (ESTc and ESTn, respectively) and the zebrafish embryotoxicity model. VPA-induced gene regulation in WEC corresponded with observed morphological effects and previously suggested mechanisms of toxicity. Gene Ontology term-directed analysis showed conservation of VPA-induced gene expression changes across in vitro-based developmental models, with ESTc and ESTn exhibiting complementary responses. Furthermore, comparison of in vitro-based developmental and non-developmental models revealed that more generalized VPA-induced effects can be detected using non-developmental models whereas developmental models provide added value when assessing developmental-specific effects. These analyses can be used to optimize test batteries for the detection of developmental toxicants in vitro.
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. ilse.tonk@rivm.nl
authors.forename: Elisa C M
authors.initials: EC
authors.lastname: Tonk
authors.forename: Joshua F
authors.initials: JF
authors.lastname: Robinson
authors.forename: Aart
authors.initials: A
authors.lastname: Verhoef
authors.forename: Peter T
authors.initials: PT
authors.lastname: Theunissen
authors.forename: Jeroen L A
authors.initials: JL
authors.lastname: Pennings
authors.forename: Aldert H
authors.initials: AH
authors.lastname: Piersma
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000187:drug effects* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D013723:Teratogens / Q000633:toxicity*; D014635:Valproic Acid / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D013723:Teratogens; D014635:Valproic Acid
keywords: Embryo; Gene expression; In vitro; Transcriptomics; Valproic acid; Whole embryo culture